Scientists discover pathogenic mechanism and novel treatment for Klebsiella pneumoniae
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Mechanisms of simultaneous linear and nonlinear computations at the mammalian cone photoreceptor synapse - Nature CommunicationsCone photoreceptors signal to several bipolar cell types at one of the most structurally complex synapses in the central nervous system. Here, the authors show how the 3D organization of this synapse creates different signals in the postsynaptic OFF bipolar cell types.
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The Outlast Trials' opening moments are beyond terrifying, but it loses steam fast in multiplayerNoah Smith is a freelance writer based out of Alberta, Canada. Noah's grab bag of non-gaming interests and passions includes Japanese mecha anime, miniature painting, as well as history, literature, and classical music. Noah also moonlights as a bureaucrat and amateur historian.
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Mechanisms of simultaneous linear and nonlinear computations at the mammalian cone photoreceptor synapse - Nature CommunicationsCone photoreceptors signal to several bipolar cell types at one of the most structurally complex synapses in the central nervous system. Here, the authors show how the 3D organization of this synapse creates different signals in the postsynaptic OFF bipolar cell types.
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CDC reports on vaccine effectiveness of bivalent COVID-19 vaccine among vaccinated vs. unvaccinated adults aged ≥65 years in 2022-23CDC reports on vaccine effectiveness of bivalent COVID-19 vaccine among vaccinated vs. unvaccinated adults aged ≥65 years in 2022-23 CDCMMWR vaccine effectiveness vaccineeffectiveness covid COVID19 SARSCoV2 unvaccinated vaccinated bivalent
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Polymyxin B therapy based on therapeutic drug monitoring in carbapenem-resistant organisms sepsis: the PMB-CROS randomized clinical trial - Critical CareBackground The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. Methods In China’s Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration–time curve across 24 h at a steady state (ssAUC0–24) of 50–100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. Results This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan–Meier’s 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0–24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. Conclusion A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results
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